Search PubMed⌕ Search

Biomedical subjects

J Ross

Publications and source records attributed to J Ross.

At least 37 records · Page 2Linked to original sources
PubMed2001

Heart-targeted overexpression of caspase3 in mice increases infarct size and depresses cardiac function.

Up-regulation of proapoptotic genes has been reported in heart failure and myocardial infarction. To determine whether caspase genes can affect cardiac function, a transgenic mouse was generated. Cardiac tissue-specific overexpression of the proapoptotic gene Caspase3 was induced by using the rat promoter of alpha-myosin heavy chain, a model that may represent a unique tool for investigating new molecules and antiapoptotic therapeutic strategies. Cardiac-specific Caspase3 expression induced transient depression of cardiac function and abnormal nuclear and myofibrillar ultrastructural damage. When subjected to myocardial ischemia-reperfusion injury, Caspase3 transgenic mice showed increased infarct size and a pronounced susceptibility to die. In this report, we document an unexpected property of the proapoptotic gene caspase3 on cardiac contractility. Despite inducing ultrastructural damage, Caspase3 does not trigger a full apoptotic response in the cardiomyocyte. We also implicate Caspase3 in determining myocardial infarct size after ischemia-reperfusion injury, because its cardiomyocyte-specific overexpression increases infarct size.

Animals↗
PubMed2001

Exploring the transcriptome of the malaria sporozoite stage.

Most studies of gene expression in Plasmodium have been concerned with asexual and/or sexual erythrocytic stages. Identification and cloning of genes expressed in the preerythrocytic stages lag far behind. We have constructed a high quality cDNA library of the Plasmodium sporozoite stage by using the rodent malaria parasite P. yoelii, an important model for malaria vaccine development. The technical obstacles associated with limited amounts of RNA material were overcome by PCR-amplifying the transcriptome before cloning. Contamination with mosquito RNA was negligible. Generation of 1,972 expressed sequence tags (EST) resulted in a total of 1,547 unique sequences, allowing insight into sporozoite gene expression. The circumsporozoite protein (CS) and the sporozoite surface protein 2 (SSP2) are well represented in the data set. A BLASTX search with all tags of the nonredundant protein database gave only 161 unique significant matches (P(N) < or = 10(-4)), whereas 1,386 of the unique sequences represented novel sporozoite-expressed genes. We identified ESTs for three proteins that may be involved in host cell invasion and documented their expression in sporozoites. These data should facilitate our understanding of the preerythrocytic Plasmodium life cycle stages and the development of preerythrocytic vaccines.

Amino Acid Motifs↗
PubMed2001

Separate visual representations for perception and action revealed by saccadic eye movements.

Some 30 years ago, Trevarthen [1] introduced the idea of two separate visual systems, a focal system for fine motor acts and an ambient system for gross body movements such as ambulation. More recent developments indicating anatomically and physiologically separate pathways in primate vision [2] have led to a different idea of separate visual systems, one for conscious perception and one for action [3]. It has received empirical support from several studies showing that pointing, reaching, and grasping can remain accurate while the perceived position or size of objects is subject to illusory distortion [4-6]. However, much of this evidence has been challenged on the grounds of methodological flaws, particularly failure to match perfectly the conditions for verbal and motor tasks and failure to replicate results [7-10]. Here we take advantage of the strong compression of perceived position that occurs around the time of saccadic eye movements [11, 12]. Under normal lighting conditions, stimuli flashed briefly over a wide range of spatial positions just before saccadic onset are neither seen nor reached for in their veridical positions, but are compressed toward the saccadic target. We validate the idea of separate systems by showing that, in the dark, subjects are able to point accurately to the correct target position, even though their verbal reports are still subject to compression.

Humans↗
PubMed2001

A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function.

The role of the cardiac myocyte as a mediator of paracrine signaling in the heart has remained unclear. To address this issue, we generated mice with cardiac myocyte-specific deletion of the vascular endothelial growth factor gene, thereby producing a cardiomyocyte-specific knockout of a secreted factor. The hearts of these mice had fewer coronary microvessels, thinned ventricular walls, depressed basal contractile function, induction of hypoxia-responsive genes involved in energy metabolism, and an abnormal response to beta-adrenergic stimulation. These findings establish the critical importance of cardiac myocyte-derived vascular endothelial growth factor in cardiac morphogenesis and determination of heart function. Further, they establish an adult murine model of hypovascular nonnecrotic cardiac contractile dysfunction.

Animals↗
PubMed2001

Physical injecting sites among injecting drug users in Sydney, Australia.

A sample of 200 injecting drug users were interviewed about their bodily injection sites. The mean number of injection sites ever used by subjects was 3.1, with a mean of 2.0 sites used in the previous 6 months. Sixteen percent of subjects had injected in five or more sites. Almost all (99%) had injected in the cubital fossa (crook of the arm). The next most popular site was the forearm (71%). Other sites included the hand (53%), foot (19%), leg (18%), neck (10%) and groin (6%). There was a clear progression in sites used, from the cubital fossa at initial injection to the use of sites such as the groin after 10 years of injecting. Females had used significantly more injection sites than males and reported more injection-related problems. The use of more injection sites was independently associated with a greater number of injection-related problems and a greater number of drug classes ever injected.

Adolescent↗
PubMed2001

Improvement of coronary artery endothelial dysfunction with lipid-lowering therapy: heterogeneity of segmental response and correlation with plasma-oxidized low density lipoprotein.

OBJECTIVES: This study assessed coronary artery endothelial function in patients with hypercholesterolemia before and after lipid lowering, using quantitative angiography to examine the acetylcholine (Ach) response along the entire analyzable vessel. BACKGROUND: Lipid lowering reverses endothelial dysfunction, but whether improvement occurs only in some segments and not others has not been established. Statistical correlation of improvement with specific lipid moieties remains undefined. METHODS: Quantitative angiography was performed after Ach (10(-6), 10(-5), 10(-4) M) in 29 patients with coronary atherosclerosis before and 18 +/- 5.2 months after lipid-lowering treatment (statins, bile sequestrant resins). Standard lipid moieties and markers of oxidized low density lipoprotein (LDL) (immunoglobulin G and M autoantibody titers to malondialdehyde-LDL, E06 epitope) were measured serially. RESULTS: Pre-treatment of the vessel diameters at control and with 10(-6)M, 10(-5) M and 10(-4) M Ach were 2.108 +/- 0.085, 2.086 +/- 0.087, 2.069 +/- 0.084 and 1.963 +/- 0.097 mm (M +/- SE), respectively, and increased at follow-up to 2.139 +/- 0.094, 2.119 +/- 0.086, 2.127 +/- 0.084 and 2.080 +/- 0.085 mm (p < 0.0001). Improvement in the most constricted and modest declination in the more dilated segments were observed. Change in the E06 and Apolipoprotein A-1 titers correlated with improved vasomotion (p = 0.027 and 0.005, respectively). The pre- and post-treatment levels of the E06 epitope, as well as the post-treatment IgM autoantibody titer to MDA-low density lipoprotein, also correlated (p < 0.028, < 0.001 and p < 0.004, respectively). CONCLUSIONS: Drug treatment reverses endothelial dysfunction, but the effect is heterogeneous. Most coronary segments show enhancement, while others show declination of dilation, underscoring the importance of assessing the entire analyzable artery. Improvement in vasomotion correlates most significantly with markers of plasma-oxidized low-density lipoprotein.

Acetylcholine↗
PubMed2001

Higher plant glycosyltransferases.

SUMMARY: Uridine diphosphate (UDP) glycosyltransferases (UGTs) mediate the transfer of glycosyl residues from activated nucleotide sugars to acceptor molecules (aglycones), thus regulating properties of the acceptors such as their bioactivity, solubility and transport within the cell and throughout the organism. A superfamily of over 100 genes encoding UGTs, each containing a 42 amino acid consensus sequence, has been identified in the model plant Arabidopsis thaliana. A phylogenetic analysis of the conserved amino acids encoded by these Arabidopsis genes reveals the presence of 14 distinct groups of UGTs in this organism. Genes encoding UGTs have also been identified in several other higher plant species. Very little is yet known about the regulation of plant UGT genes or the localization of the enzymes they encode at the cellular and subcellular levels. The substrate specificities of these UGTs are now beginning to be established and will provide a foundation for further analysis of this large enzyme superfamily as well as a platform for future biotechnological applications.

Amino Acid Sequence↗
PubMed2001

Palladium-catalyzed regioselective arylation of an electron-rich olefin by aryl halides in ionic liquids.

[figure: see text] Palladium-catalyzed arylation of the electron-rich olefin butyl vinyl ether has been accomplished in the ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF4]), using as the arylating agents aryl iodides and bromides instead of the commonly used, but commercially unavailable and expensive, aryl triflates. The reaction proceeds with high efficiency and remarkable regioselectivity, leading almost exclusively to substitution by various aryl groups at the olefinic carbon alpha to the heteroatom of butyl vinyl ether.

Journal Article↗
PubMed2001

Bisphosphonates in multiple myeloma.

BACKGROUND: Multiple myeloma is a disease characterized by the neoplastic proliferation of a clone of plasma cells that can lead to bone destruction. Bisphosphonates are specific inhibitors of osteoclastic activity. Therefore, there is a pharmacological basis for their use in multiple myeloma. However, the exact clinical role of bisphosphonates in multiple myeloma remains unclear. OBJECTIVES: Primary: to determine whether adding bisphosphonates to standard therapy in multiple myeloma decreases skeletal-related morbidity (pathological fractures), skeletal-related mortality and overall mortality. Secondary: to determine the effects of bisphosphonates on pain, quality of life and incidence of hypercalcemia. SEARCH STRATEGY: We searched MEDLINE (1966 - June 2001), LILACS (1982 - June 2001), EMBASE (1974 - December 2000) and the Cochrane Controlled Trials Register (all years, latest Issue 03/2001) to identify all randomized trials in multiple myeloma. All of these references were accessed in order to identify trials related to the use of bisphosphonates in myeloma. All relevant references in each article were also scanned. We also performed a handsearch of relevant meeting proceedings from 1993 to 2000. Additionally, manufacturers of bisphosphonates and researchers in the field were contacted. SELECTION CRITERIA: Randomised trials with a parallel design on the use of bisphosphonate in myeloma compared with placebo or no treatment as a control group. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility, methodological quality and abstracted data. A third reviewer checked all data after the extraction was completed. Statistical heterogeneity was tested using random and fixed effect models. All pooled data are reported using Peto odds ratios and, when appropriate, as absolute risk reduction and the number needed to treat to prevent or to cause a pathological event. MAIN RESULTS: Eleven trials were included with 1113 patients analysed in bisphosphonates groups, and 1070 analysed in control groups. There was no significant statistical heterogeneity among trials for the endpoints selected for comparison in this review. The pooled analysis of the published evidence demonstrated the beneficial effect of bisphosphonates on prevention of pathological vertebral fractures [OR=0.59 (95% confidence interval (CI) 0.45-0.78); P=0.0001] and on amelioration of pain [OR = 0.59 (95%CI 0.46-0.76); P=0.00005]. However, the analysis of the effect of bisphosphonates on pain was based on clinically heterogeneous data and must be interpreted with caution. Although there was no statistical heterogeneity between groups, the benefit was most apparent with clodronate and pamidronate. In absolute terms, the result may be interpreted to mean that 10 (95%CI 7-20) patients with multiple myeloma should be treated to prevent one vertebral fracture, and 11 (95%CI 7-28) to prevent one patient experiencing pain. We found no significant effect of bisphosphonates on mortality, on the reduction of non-vertebral fractures or on the incidence of hypercalcemia. There were no significant adverse effects associated with the administration of bisphosphonates. Our results are based on the extraction of published data, which were sometimes poorly reported, and thus the results should be understood as the best possible summation of available evidence. REVIEWER'S CONCLUSIONS: Adding bisphosphonates to the treatment of myeloma reduces pathological vertebral fractures and pain but - from the published evidence - not mortality. On current evidence, clodronate or pamidronate may be the preferred agents.

Bone Diseases↗
PubMed2001

Multiplex PCR amplification of eight STR loci in Austrian and Croatian Caucasian populations.

Austrian and Croatian Caucasian population data were generated for eight tetrameric STR loci amplified in a single multiplex reaction. Fluorescent detection was employed using the ABI Prism 310 Genetic Analyzer, the 377 DNA Sequencer (ABI) and the 373A DNA Sequencer (ABI). The loci analyzed were HUMvWFA31 (vWA), HUMTH01, HUMTPOX, HUMCSF1PO, D5S818, D13S317, D7S820 and D16S539 as part of the GenePrint PowerPlex multiplex system.

Alleles↗
PubMed2001

Cardinal axes for radial and circular motion, revealed by summation and by masking.

Both electro-physiological and psychophysical studies point to the existence of detectors specialised for the analysis of optic flow. However, it is unclear whether these detectors are tuned to specific 'cardinal directions' (such as radial and circular motion), or whether they respond equally to all directions of optic-flow motion, including intermediate spiral motions. Here summation and masking studies of motion coherence sensitivity are reported that suggest that optic flow may be tuned to radial and circular cardinal directions. Strong summation was found between two orthogonal directions of spiral motion, but much weaker summation between radial and circular motion. As orthogonal spiral motions always contain a common radial or circular component, the stronger summation for these motions implies that detectors are tuned to radial and circular directions. Similarly, the most effective masking stimuli (placed adjacent to but not superimposed on the test stimuli) tended to be those in the radial or circular directions, even for spiral targets, further suggesting that flow-field motion is detected and discriminated by mechanisms tuned to these 'cardinal' directions.

Discrimination, Psychological↗
PubMed2001

Changes in visual perception at the time of saccades.

We frequently reposition our gaze by making rapid ballistic eye movements that are called saccades. Saccades pose problems for the visual system, because they generate rapid, large-field motion on the retina and change the relationship between the object position in external space and the image position on the retina. The brain must ignore the one and compensate for the other. Much progress has been made in recent years in understanding the effects of saccades on visual function and elucidating the mechanisms responsible for them. Evidence suggests that saccades trigger two distinct neural processes: (1) a suppression of visual sensitivity, specific to the magnocellular pathway, that dampens the sensation of motion and (2) a gross perceptual distortion of visual space in anticipation of the repositioning of gaze. Neurophysiological findings from several laboratories are beginning to identify the neural substrates involved in these effects.

Animals↗
PubMed2001

Adult mice deficient in actinin-associated LIM-domain protein reveal a developmental pathway for right ventricular cardiomyopathy.

Although cytoskeletal mutations are known causes of genetically based forms of dilated cardiomyopathy, the pathways that link these defects with cardiomyopathy are unclear. Here we report that the alpha-actinin-associated LIM protein (ALP; Alp in mice) has an essential role in the embryonic development of the right ventricular (RV) chamber during its exposure to high biomechanical workloads in utero. Disruption of the gene encoding Alp (Alp) is associated with RV chamber dilation and dysfunction, directly implicating alpha-actinin-associated proteins in the onset of cardiomyopathy. In vitro assays showed that Alp directly enhances the capacity of alpha-actinin to cross-link actin filaments, indicating that the loss of Alp function contributes to destabilization of actin anchorage sites in cardiac muscle. Alp also colocalizes at the intercalated disc with alpha-actinin and gamma-catenin, the latter being a known disease gene for human RV dysplasia. Taken together, these studies point to a novel developmental pathway for RV dilated cardiomyopathy via instability of alpha-actinin complexes.

Actinin↗